A total of 343,864 human duplication-inferred mutations from intergenic regions of segmental duplications satisfied the criteria we established for reliable DIM inference in DNA duplicon sequence alignments (see Figure 1 and Methods).
However, only ~12% of all human duplications resulted from misalignment of two repeat elements [ 22], refuting the importance of repeat sequences in the production of duplications.
The vast majority of these paralogues pairs have accumulated even fewer silent substitutions (K S < 0.015), indicating that most human duplications occurred only in the past 3 4 million years, after the divergence of Homo and Pan lineages.
Human segmental duplication content of inversion breakpoints was determined using the whole genome assembly comparison approach (44).
These truncated genes could act as partial competitive inhibitors of the parent gene, as seen with the human specific duplication of the SRGAP2 gene, which in turn causes slower brain development in humans relative to other mammals [ 29].
Given that these subtle alterations in expression of the conditional allele partly mimic the effect of the human EFNB1 duplication, we investigated the craniofacial phenotypes of Efnb1Lox/+ mice in greater detail.
The locations and alignments of human segmental duplication events greater than 1 kb in length and over 90% identical between regions were obtained from http://humanparalogy.gs.washington.edu/build36/align_both/ (last accessed July 1 , 2014 (She et al. 2004b).
Based on this fact, we have developed a computational scheme for inference of point mutational events in human segmental duplications, which we collectively term duplication-inferred mutations (DIMs).
Human segmental duplications are frequently found within complicated mosaics of duplicated fragments (Bailey and Eichler, 2006).
We identified 111 potentially Neandertal-specific segmental duplications (average size 22,321 bp and total length 1862 kb) that did not overlap with human segmental duplications (fig. S20).
